The latest edition of Nightwalkers, the US RLS foundation magazine, reports that Prof. Stefan Clemens of East Carolina University has applied for a patent to use Ecopipam to treat augmentation of RLS symptoms on dopaminergic drugs.
He has licensed the product to Emalax Biosciences and trials will happen soon.
Dopaminergic drugs affect the D2 and D3 dopamine receptors and stop them being over excited. However, over time the D1 receptors then become over excited and cause augmentation ( worsening of symptoms). Ecopipam targets the D1 receptors and calms them, apparently alleviating augmentation.
It is early days, but if Ecopipam does indeed work to stop augmentation, it would be life changing for RLS patients.
There are so few research studies or trials of new medications so this is encouraging.
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Joolsg
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None of both Madlegs. I read the proposal and the initial study. Sort of. DAs target mainly the D2 and D3 receptor that have an inhibitory function. When or while the receptors get reduced due to DA use, the excitatory D1 receptors tend to increase. Dopamine agonists activate. Thus when a DA initially activates the inhibitory (translate here as calming) function, the later increase in D1 receptors take over and the excitative functioning overrides the inhibitory functioning. This is in my own words and understanding.
Now ecopipam antagonises (read: stops the functioning of) D1 and D5 receptors. Hence the potential of reversing the overriding excitatory functioning of the D1 receptors allowing the inhibitory functioning if the D2 and D3 receptors to do their thing.
I hope this helps. It may not be exact, but this gives an idea. It does brings hope to elongate the efficacity of the DAs.
The new studies also aim at designing a more specific D1 antagonist.
Thanks for this Jools, it sounds absolutely major in the handling of DA's. Do you think, if the drug works as intended, that DA's will be back on the menu, or too risky?
I suspect that they could go back on the menu for those who don't respond to gabapentin and pregabalin and who have bad side effects to opioids. There are so many people who get total relief from RLS on opioids but the side effects of severe insomnia, nausea or anxiety are intolerable. I don't think DAs should ever be back as first line treatment
Thanks for posting this information Joolsg. This has the possibility to help thousands of sufferers. It gives me hope that the medical profession is not leaving us out here to die.
Sounds scary. DAs cause other side effects than augmentation, what side effects and or long term things will this new drug cause? My rls has changed since augmenting and withdrawaling from DAs. I think that my symptoms would not be this bad had I never taken those horrible drugs!
Interestingly, my experience runs counter to that Jools. I had an iron infusion well before I started any medications for PLMD/RLS. That iron infusion wasn't effective.
I then took pramipexole for approximately one year until augmentation set in. From memory the dose was 500mcg. (I had no trouble whatsoever withdrawing from pramipexole).
Then I went on pregablin which has worked well in the main but after 7 years on it, i'm not so sure that is still the case.
And to WideBody; I felt the diprydiamole made a difference for the brief time I was on it.
Thanks Amrob. Very interesting. Clearly it doesn't seem to matter whether you've been on meds. Iron won't help 20 per cent regardless. Hope you find an alternative med to pregabalin OR that an increase helps.
hi you are so lucky not too have had withdrawal symptons from pramipexole i have ceased taking it after having RLS in my arms and torso my arms had a mind of their own i am in my 8th night without Sifrol i tell you it is hell at night. i take 150 mg of lyrica which doesnt work i guess which is why i am sat here at 3.08am
We all feel you. Consider ordering Kratom powder-it will get you through this and you won't have such horrible nights! It literally stops rls in minutes. Or, if you can get someone to prescribe an opioid, that would help you. But, that can take weeks to months...or....never come to fruition at all!
Amrob-I think the difference is that many of us were on DA's for a large number of years. We are the ones that have an extra tough time finding something that works. Especially something natural. Sadly!
Opioids are often the only answer and hence Dr. B's reluctance to recommend other solutions-even Dipyridamole.
I am taking berberine and trying THC and various other things with the wild hope that I can change these facts. It may be a long shot but I am trying.
I hope you continue to have something that works for you!
Sounds promising but my concern is how long it takes for long-term side effects to emerge. I didn't know for decades that my antidepressant was provoking my RLS. I thank God that I didn't know because certainly I would have been prescribed a DA as a "remedy." When pharma creates the long-term problem and pharma invents the solution, I'm leery. I'd love it to succeed - but it may take a v-e-r-y long time to be certain.
Agreed. Dopamine agonists were trialled for 12 weeks and it was a decade later that the hundreds of thousands of cases of augmentation became apparent.
I justify read your post and am interested in the magazine that you “mentioned “, Night walkers”. In addition to MS I have severe RLS @ am interested in receiving said magazine. Could you please provide mailing address.
Hindsight is a wonderful thing. Obviously I would NEVER have taken dopamine agonists if I had known what they would do further down the line.Gabapentin didn't work for me. Dr. Buchfuhrer said it doesn't work for many who had severe augmentation and withdrawal.
I'm now on 0.4mg Buprenorphine at night & it is miraculous.
I used a DA for over 14 years with very few side effects. It worked brilliantly. However, augmentation set in so I had to withdraw. Worst 4 months of my life. Anyway any potential to be able to use DAs without augmentation would be amazing.
Help! I just found this group and, from what I’m reading, I believe I am in augmentation. After three years and three increases in dosage of pramipexole, my NP told me Thursday to stop taking it and start ropinirole. I almost lost my mind last night and slept maybe 90 minutes total. I wasn’t too bad today, but tonight I’m losing it again - no more dosing until 8:00 AM. What can I do?? I’ve been pedaling on an exercise bike, but I’m exhausted. I’m kicking and pacing and jerking and stretching…
Get a new doctor asap. Once you suffer automatically, the ONLY solution is to slowly reduce Pramipexole and never touch another dopamine agonist. Putting you on Ropinirole will just prolong the agony. Go back on the dose of Pramipexole you were taking (the absolute max dose is 0.5mg but experts say no more than 0.25mg). Reduce by half a 0.088mcg/0.125mg pill every 2 to 3 weeks and you'll probably need a low dose opioid and cannabis to help the withdrawal symptoms.Find an RLS specialist. Where are you?.Presumably not here in the UK.
Withdrawal is really tough but once off dopamine agonists, your daytime RLS will disappear and alternative meds should cover nights.
Pregabalin or gabapentin are the usual meds given after Pramipexole. Start 4 weeks before last dose of Pramipexole.
Ensure serum iron is above 60 and serum ferritin above 100, preferably 300. Naka sure you're not on any meds that trigger/worsen RLS like anti depressants, anti histamines, statins, beta blockers, PPI meds.
Thank you for replying! I’ve had three increases in dosage during the past three years- now up to .5 mg twice a day. Last night I did break down and take my pramipexole around 3:00 AM. I took half my regular dose (broke a .5 mg pill) at 10:00 AM and have slept all day - still groggy. I am a 25+ year Prozac user. From what I am learning, I need to get off that too! I am in a rural area, two hours from a “city doctor”, but I am determined to get my life back. I am in misery. Thank you again for the information.
Yes Prozac triggers RLS. I know of many people who have managed to get off Pramipexole and their anti depressants and are RLS free.Reduce one drug at a time. The slower the better.
No need to suffer this much...consider ordering Kratom powder so you can get some sleep! As I posted above-it works within minutes. It's not perfect but will definitely and literally save your sanity. Best of luck!
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